A Call to Action

Children – The missing face of AIDS

Paediatric Care and treatment:

What do we know and what needs to be done?

Dr Helene Möller, (M.Pharm, PhD)Field Support Officer HIV/AIDSUNICEF Supply DivisionCopenhagen

Dr Chewe Luo, (MD(Pead), MTropPead, PhD)Senior Program AdviserUNICEF Programme DivisionNew York

The growing numbers of adults and children* living with HIV (UNAIDS

2005)

0

5

10

15

20

25

30

35

40

45

19861987198819891990199119921993199419951996199719981999200020012002200320042005

Oceania

North Africa & Middle East

Eastern Europe & Central Asia

Western and Central Europe and North America

Latin America and Caribbean

Asia

Sub-Saharan Africa

Millions

Number of people living with HIV

* under 15 years old

2001 United Nations Global Assembly Special Session on HIV/AIDS: PMTCT Targets

Reduce the proportion of infants infected with HIV by 20% by 2005 and 50% by 2010, by:

• Ensuring that 80% of pregnant women accessing antenatal care receive information, counseling and other HIV prevention services

• Increasing the availability of and providing access for HIV-infected women and babies to effective treatment to reduce MTCT of HIV…

Global PMTCT Response (2004)Countries with PMTCT programs per region

101

39

25

16

15

6

16

2

6

6

2

0

0 20 40 60 80 100 120

Total

Sub-Saharan Africa

Latin America and Caribbean

CEE/CIS

Asia South, East and Pacific

North Africa & Middle East

Countries with PMTCT Programs National Service Coverage

Source: United Nations Children Fund Annual Reports, 2004

10% of women giving birth annually are counseled / tested for HIV: Data from 53 high

burden countries (UNICEF December 2005 PMTCT Report Card)

8,403,718

7,896,717

Women counseled on PMTCT Women tested for HIVUNICEF PMTCT Report Card 2005

Only 9% of HIV-positive women globally receive ARV prophylaxis

(UNICEF December 2005 PMTCT Report Card)

92%

45%

17%11%

3%

78%

27%

11%7%

1%0%

10%20%30%40%50%60%70%80%90%

100%

Central andEastern Europe

Latin America East andSouthern Africa

Asia West andcentral Africa

HIV-positive women identified HIV-positive women given ARVs

Figure 4: Proportion of women receiving ARV prophylaxis in 10 highest burden countries accounting for two thirds of all MTCT infections in

2004

0%

20%

40%

60%

80%

100%

Nigeri

a (0.1

%)

DR Co

ngo (0

.8%)

Ethiop

ia (1%

)

Tanza

nia (2

%)

Mozam

bique

(3.2%

)

India (

3.5%)

Zimbab

we (5%

)

Zambia

(16%

)

Keny

a (20

%)

SouthA

frica (

22%)

Perc

enta

ge

Received ARV prophylaxis Did not receive ARVs

2.3 million HIV-infected women give birth every year…

Western & Central Europe

200200[< 400][< 400]

North Africa & Middle East8 9008 900

[2 600 – 30 000][2 600 – 30 000]

Sub-Saharan Africa630 000630 000

[560 000 – 740 000][560 000 – 740 000](90%)(90%)

Eastern Europe & Central Asia3 7003 700[2 600 – 6 400][2 600 – 6 400] East Asia

2 3002 300[840 – 6 300][840 – 6 300]South

& South-East Asia44 00044 000[25 000 – 83 000][25 000 – 83 000]

(6%)(6%)Oceania1 1001 100

[230 – 4 800][230 – 4 800]

North America500500

[<1 000][<1 000]

Caribbean3 8003 800

[2 000 – 8 000][2 000 – 8 000]

Latin America7 7007 700

[5 600 – 14 000][5 600 – 14 000]

Total: 700 000 (630 000 – 820 000) Source: UNAIDS, 2005 Report on the global AIDS Epidemic, UNAIDS,

Geneva, 2005

Estimated number of children (<15) newly infected in 2005

Estimates of children in need of ARV treatment and cotrimoxazole

(UNAIDS/UNICEF 2005; Boerma et al, WHO Bulletin 2006)

2005 estimates

Child (0-14 years) deaths due to AIDS

Children (0-14 years) in need of ART

Children (0-18 months) in need of ART

Children (0-14 years) in need of cotrimoxazole - diagnosis at 18 months

Children (0-14 years) in need of cotrimoxazole - diagnosis before 18 months

Global 410,000 660,000 270,000 4,000,000 2,100,000

Caribbean 3,100 5,100 1,800 29,000 15,000

East Asia 1,500 1,900 1,700 17,000 7,600

Eastern Europe & Central Asia 1,100 1,600 1,100 18,000 6,200

Latin America 6,000 8,600 400 70,000 35,000

North Africa & Middle East 5,300 7,600 4,400 59,000 18,000

Oceania <500 <500 <500 2,000 <1000

South & South East Asia 26,000 37,000 21,000 290,000 130,000

Sub-Saharan Africa 370,000 600,000 240,000 3,500,000 1,900,000

PEPFAR countries 250,000 410,000 200,000 2,400,000 1,300,000

Asia 28,000 39000 23000 310,000 140,000

Latin America & Caribbean 9,200 14,000 5,800 100,000 50,000

Paediatric Care and treatment:

What do we know What needs to be done?

Lack of attention to children- What do we need to consider in this consultation?

• Children are not little adults and the guidelines need that specificity

• Disease more aggressive in children – 30% mortality at yr 1, 50% at yr 2 and 60% at yr 5 – aspects of early diagnosis to be considered• HIV Diagnosis for children below 18 months problematic:

• Clinical disease presentation non-specific• PCR expensive and requires sophisticated labs and expertise

• Laboratory monitoring in children under 6 years difficult –CD4% required for children below 6 years

• Capacities and expertise on care and treatment underdeveloped

• Lack of infrastructure for chronic care management of children

Early diagnosis of HIV infection

Ensure reliable early diagnosis of HIV infected children:- Ensure specialized care for infected children- Discontinue PCP prophylaxis in uninfected children- DNA PCR (real time PCR) on Dried Blood Spots (on filter

paper) performed in regional/national centers?

A pilot program to make available early HIV diagnosis in all hospitals in northern Thailand (collaboration Faculty of Associated Medical Science - PHPT - CDC Region 10; support: Sidaction)

Children do well on ART: Evidence from a randomised trial

P Fassinou et al AIDS 2004, 18:1905 -1913

Children do well on treatment:Evidence from the Brazilian National Program

(Matida L et al, 2002)Kaplan-Meier survival estimates, by anodiag

analysis time0 50 100 150

0.00

0.25

0.50

0.75

1.00

1997 - 19981995 - 19961993 - 19941988 - 1992Before 1988

Years from randomisation

Systematic delivery of cotrimoxazole prophylaxis can improve children’s lives-

CHAP Trial (Chintu et al Lancet 2004)

Prop

ortio

n al

ive

Cotrimoxazole

Placebo

0.40

0.60

0.80

1.00

0 .5 1 1.5 2

232 177 106 47211 143 72 29

HR=0.57[0.43-0.77] p=0.0002

Global causes of U5 Mortality: How do Global causes of U5 Mortality: How do we address Paed HIV Care within the we address Paed HIV Care within the

broader context of child survival ?broader context of child survival ?

Under-nutrition is an underlying cause of 53% of deaths of children under five years of age

Source WHR 2005

What should be our guiding principles?

• Urgency. There is an immediate need to scale up diagnosis and treatment. To achieve this guidelines should consider what can be delivered at the lower levels and different practitioners.

• Equity of Access. All children in need of treatment, care, and support, including the hard to reach will receive it.

• The Centrality of the needs Children Living with HIV/AIDS. The needs of children living with HIV/AIDS and their caregivers within the broader context of child survival.

• Delivery of Life-Long Care and Support. Once started, antiretroviral therapy is for life. Recommendations should be realistic to ensure uninterrupted medicine supply.

Procurement and Supplies Management

PMTCT Scale UpWhat tools do we have ?

WHO PMTCT guidelines: Discussions in Montreaux June

2005…. SUPPLY OPTIONS

MOTHER BABY

nvp 200mg - single dose

zdv 300mg - from 28 weeks

zdv/3TC - intrapartum and then for 7 days

nvp susp 0,6ml single dose

zdv oral liquid for 7 days

zdv oral liquid for 28 days

FORMULATIONS TO PROVIDE PMTCT SERVICES : Key challenges

• Nevirapine tablets: • Commercially available as pack of 60 tablets• Blister packs facilitate dispensing to some extent• For PMTCT, need 1 tablet stat, often to take home ?

• Nevirapine suspension (10mg/ml):• Commercially available as 240ml• Donation programmes supply 20ml or 25ml• For PMTCT, need 0,6ml per day ?

• Commercial bottles are adapted with fitted caps to facilitate dispensing, donation to decant ?

• Dispensing syringe : BAXA Donation

FORMULATIONS TO PROVIDE PMTCT SERVICES : Key challenges

• zidovudine tablets: bd from 28 weeks• Commercially available as pack of 60 tablets• Blister packs facilitate dispensing to some extent

• zdv 300mg/3TC 150mg tablets: intrapartum, bd 7 days• Commercially available as pack of 60 tablets• Blister packs facilitate dispensing to some extent• For PMTCT, need 16 – 18 tablets per week, 20’s pack ?

• zidovudine oral liquid (10mg/ml)• Commercially available as 100ml, 200ml, 240ml bottle• For PMTCT, need approximately 35 – 50 ml per week, or• 150ml per month ( if mom had no ART ) ?

Procurement and Supplies Management

Paediatric HIC Care and Support

Global technical tools available ..

1. 2006 ART treatment guidelines for paediatric and adult ART; and ARVs for PMTCT (2004)

2. Guidelines on care treatment and support of HIV infected women and their children (nutrition, diagnosis, care of HIV exposed and infected children)

3. Global strategy on infant and young child feeding (range of tools)

4. Expert recommendations on Appropriate Paediatric ARV Formulations

Global technical tools available ….

5. Recommendations on use of cotrimoxazole for HIV exposed and infected infants

6. Revised clinical staging of HIV infection for use in children (& adults)

7. Technical reference groups for paediatric HIV care, ART & PMTCT

8. Simplified standardised training tools for integrated HIV care (IMAI - ART care for children and adults, IMCI)

9. Programme indicators for paediatric HIV & ART care & PMTCT

COTRIMOXAZOLE PROPHYLAXIS

DOSE

Syrup(40mg/200mg)

Paediatric tablet

(20 mg/100 mg)

Single Strength Adult Tablet(80 mg/400mg)

Double StrengthAdult Tablet(160 mg/800 mg)

< 6 months20 mg TMP/100 mg SMX

2.5ml 1 n/a n/a

6 months – 5 years40 mgTMP/200mg SMX

5 ml 2 1/2 n/a

> 6 – 14 years80 mg TMP/400 mg SMX

10 ml 4 1 1/2

> 15 years(or >35 kg )160 mg TMP/800 mg SMX

n/a n/a 2 1

FIRST LINE REGIMENS Operational Characteristics of available ARVs

TreatmentProducts available

(volume)Storage & other considerations

1st Line Innovator GenericFridge

? Other

ZDV 240ml 100, 200ml No

d4T 200ml - Yes Supplied as pwdr

3TC 240ml 100, 240ml No

NVP 240ml20*, 25,100,

240ml NoSome non-WHO PQed formulations as powder

EFV 180ml Coming soon No Not for children under 3yrs

* Only available in donation programme, with dispensing syringe

SECOND LINE REGIMENSOperational Characteristics of available ARVs

TreatmentProducts available

(volume)Storage & other considerations

2nd Line Innovator Generic Fridge ? Other

ABC 240ml - No Abacavir Hypersensitity

ddI 237ml - NoNeed antacid,

4g in 237ml not available

LPV/r 5x60ml - Yes, new?Need cold shipment,

alcohol, new on the way

NFV 144g pwd - NoDifficult to dispense

Crushed tablets cheaper

PROPOSED REVISIONS: 1st and 2nd Line Regimens

1st Line Regimen

RTI based

2nd Line RegimenRTI PI *

ZDV/d4T + 3TC + NVP/EFV ddI + ABC

LPV/r orSQV/ror NFV

ABC + 3TC + NVP/EFV ddI + ZDV ± 3TC

ZDV/d4T + 3TC + ABC EFV or NVP ± ddI or EFV or NVP ± 3TC

MSF PAPER 2004: Current situation regarding prices and availability of specific children formulations …

• Cost of treatment drops when switching to adult formulations: Peak around 14kg bodyweight

• Using tablets for a child (20 kg) reduces the cost per treatment per year nearly 8 times:• (d4T / 3TC / NVP )

Best generic price/y $ 566 $224Best innovator price/y $1,706 $631

• Managing the switch – increases complexities in resource poor settings

WHAT IS NEW ?WHO 6th Expression of Interest spells it out

• Single formulations, adults, adolescents, paeds:• NRTIs; ABC, ddI, 3TC, d4T, TDF, ZDV• NNRTIs ; NVP, EFV• PIs; IDV, NFV, SQV, rtv

• Reduced doses, scored tablets for the young, liquid formulation

• FDC for adults and paeds, scored• Co-packaged formulations for adults and kids

Procurement and Supplies Management

The need for Optimising Supply and

Demand

Challenges affecting supply strategies supporting global

disease programmes• Product selection is driven working groups,

consultants and prequalification efforts• Lack of consideration of product specifications, e.g. expiry

dates, weights and volume• Lack of consideration of storage and distribution

requirements• Lack of consideration of performance characteristics, e.g.

refrigeration needs• Lack of consideration of costs and cost drivers, buffer stock• Push to place orders to reach programme targets

Challenges affecting supply strategies supporting global

disease programmes• Traditional planning methods are focussed on

pushing products downstream towards end users, rarely with an understanding of the true demand at the first level of care

• Push to place orders• Items move from under-stock to overstock in no

time, expire, move back to undersupply Erratic demand

• Affecting private sector as much as public

Delivery Systems & Management structures drive

supply and demand• Unclear scientific data on effective models for delivery of paediatric care in resource limited settings

• Chronic care management of sick children limited in most settings

• However, best practices from programmatic experiences are emerging

Optimising identification of children and entry into chronic paediatric care

and treatment

Pediatric HIV CST program

PMTCT Services

In and outpatient units

Home Based CareNutrition Rehabilitation Centers

Referral from other units

(VCT, TB units, adult ARV clinics)

Tiered decentralised model in Brazil: What should be delivered

at what level•Universal•Regionalized•Hierarchical•Integrated

Hom

e C

are

Hospitals

Day clinics, Outpatient clinics

Primary care units

Thank You